Replies to post #293281 on NorthWest Biotherapeutics Inc (NWBO)

[biosectinvestor]

Thank you Lykiri. Yes, I had originally, way back when I first started posting here, includes a post with a bunch of links on German legal/ethical considerations post WWII but probably someone found some minor TOS violation and got that one post deleted at the time.

The Germans have a history that makes this a huge, hot button issue, exactly as you suggest. And often placebos are used where you expect a very minor difference to be made by the treatment, for instance where you actually expect maybe just a few months difference. With some cancer drugs they might’ve seen only 3 months difference, overall. So the placebo group really brings that out. But I think people were seeing things with DCVaxL that really caused ethical concerns for the placebo arm. Just my opinion.

And then when you line up many other indicators, I think it just starts to look quite clear to me, again, just my opinion, but rationally, it starts to just add up, point-by-point-by-point.

GLTA! :)

[sentiment_stocks]

If Germany felt that the placebo arm was not ethical - assuming they knew that DCVax worked (and their number explains the exact number of missing patients in the trial) - then they chose not to enroll those placebo patients in the trial.

However, those placebo patients would have had the opportunity to cross over upon progression. Additionally, those patients would have had their vaccines made.

So if this is how it happened, then how were these 17 placebo patients with vaccines made handled? Were they put into the EAP trial? Or told they couldn't enter the trial?

We remember the patient in Germany who's wife thought that he was to have been a placebo patient in the trial, but that he was unable to enter. Had he entered into the EAP and received the vaccine at once, I don't think she would have written that blog post in the manner she did, implying, as memory serves, that her husband did not receive DCVax, nor enter the trial.

So that would be a pretty bad, mean spirited decision, to my thinking anyway, if those 17 potential placebo patients were basically unable to enter the trial, nor the EAP trial, because DCVax works.

And this would have all taken place, presumably, without the company knowing it?

There are square pieces that aren't fitting into the circle holes here.

I realize, of course, to reiterate, that the numbers mathematically work out perfectly, which is bizarre. And for those who don't know what we're talking about, here it is:

The trial was supposed to enroll 348 patients.

Instead, after the screening halt, the number of patients were reduced to 331. We think there were about 31 patients who entered the trial after the screening halt as they were already in the screening pipeline (in August 2015) and their vaccines were made.

Later when the journal article came out, it revealed that there were 232 treatment patients, but only 99 control patients, equaling 331.
https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-018-1507-6

However, 232 treatment patients was the correct number of patients who should have been enrolled in the trial, had it enrolled to the full amount of 348. The trial was supposed to enroll 2:1 (2 treatment to 1 control). So 348/3 = 116; thus 116 was to be the control number, and 116 x 2 or 232 of treatment patients.

So 116 supposed-to-be-control patients - 99 control = 17 patients.
and
348 - 17 = 331 (the number of patients now in the trial)

We should note that LG and DI have insisted rather profusely that this is all coincidence and that everyone was randomized as the trial had planned.

[MI Dendream]

Lykiri, thanks for your DD on the cause of the halt and German regs!

There is no other sensible explanation that has been given that can account for a halt in new screening that allows:

1) patients randomized to treatment to complete their treatment
2) Placebo patients to continue to cross over (1&2 negate a safety issue)
3) patients that have been screened to enroll in the trial (this one negates any manufacturing problem argument)
4) the final 32 patients enrolled to be placed on therapy only (this is where the ethics comes into play)
5) the power of the study to be reduce by #4 action
6) the halt to be lifted in Feb 2017
7) the silence of the company regarding the reason for a halt

I believe we have a layup for The primary PFS endpoint. The long delay between 233 deaths and data lock should produce a big fat tail that ensures the HR OS vistory.

Folks, we have a winner!